A new anti-tumour drug of marine origin

Natural products from plants and microorganisms have been the cornerstone of anti-cancer pharmacology since the very beginning of industrial development and are still used today for the treatment of cancer patients. The sea is a vast source of biodiversity which is yet to be fully exploited by modern pharmacology. A Spanish company, leader in the discovery and development of new drugs of marine origin has several compounds in its pipeline as potential anti-tumour agents. One such compound, trabectedin, was recently approved in Europe and in several other countries for the treatment of soft tissue sarcoma and ovarian cancer, and is the first anticancer drug of marine origin to have reached the market.

Paola Allavena, Principal Investigator of Laboratory of Cellular Immunology explains: “As an anti-tumour agent, trabectedin kills tumour cells and blocks their proliferation by interacting with DNA. Trabectedin, however, is more than a conventional cytotoxic agent. Scientists in Milano, coordinated by myself at Humanitas and by Maurizio D’Incalci at the Mario Negri Institute for Pharmacological Research, in collaboration with the Tumour Institute, have now discovered that trabectedin has additional mechanisms of action and its anti-tumour efficacy relies also on the ability to target the tumour microenvironment. Specifically, trabectedin kills a subset of immune cells (macrophages) that populate the tumour tissue and are known as tumour-associated macrophages (TAMs). These immune cells, instead of defending the body, as they should do, have been corrupted by tumours and help cancer cells in several different ways, for instance by producing growth factors that stimulate tumour proliferation and the development of new vessels, or tumour cell spreading. In the last decade, it has become increasingly clear that the presence of TAMs in the tumour microenvironment is significantly associated with resistance to chemotherapy and disease progression.

The study, published in Cancer Cell, shows that trabectedin is able to kill macrophages and their precursor cells (circulating monocytes) while sparing other immune cells. In patients with soft tissue sarcoma, trabectedin reduces the number of TAMs and inhibits their pro-tumour activities. The new results demonstrate that trabectedin has dual anti-tumour effects: it targets both cancer cells and the pro-tumoural TAMs. These findings disclose a new mode of action of a clinically useful and already available anti-cancer agent, and open new perspectives for the exploitation of this unique property in therapeutic settings”.